Chemistry: analytical and immunological testing – Hemoglobin – myoglobin – or occult blood
Patent
1993-08-30
1995-06-27
Housel, James C.
Chemistry: analytical and immunological testing
Hemoglobin, myoglobin, or occult blood
436164, 436171, G01N 3372
Patent
active
054279518
DESCRIPTION:
BRIEF SUMMARY
This invention relates to a diagnostic test suitable for monitoring the occurrence of a heart attack, or the total plasma antioxidant status as a marker of predisposition to such an event.
The invention therefore arises out of the need to clarify firstly the diagnosis of chest pain in patients as a myocardial infarction and, secondly, the potential for early monitoring of predisposition to heart disease through assessment of total plasma antioxidant capacity.
BACKGROUND OF THE INVENTION
There is a need for means for monitoring plasma antioxidant status, particularly that of a patient believed to be at risk of a heart attack. Further, there is a corresponding need to monitor whether myocardial infarction has actually occurred in a suspect heart attack patient, as it is not always possible for the clinician to distinguish between the experience of chest pains due to less serious disorders and those associated with a heart attack. In both instances, i.e. before or after such an event, knowledge is needed in order to determine the appropriate therapy.
Tests are already known to determine whether myocardial infarction has occurred. Thus it is recognised that such an event causes the early release of the haem protein myoglobin into the plasma (see Drexel et al., American Heart Journal, 105, No. 4, 642-650). The appearance of myoglobin as an indicator of myocardial infarction has been previously determined by radioimmunoassay (Rosano & Kenny, Clin. Chem. 23, 69-75, 1977) and by an agglutination test using a commercially available polystyrene latex sensitised with myoglobin antibodies. The disadvantages of such tests are that radioimmunoassays are time-consuming and thus not suitable for emergency testing, while latex agglutination tests give only semi-quantitative results and can occasionally give false negatives in the presence of antigen excess. It is also possible to detect the leakage of other enzymes such as creatine kinase but these enzymes are released more slowly than myoglobin. The presently available detection kits are costly, lacking in precision or involve time delays so that the diagnosis of a heart attack cannot be confirmed until many hours after the event.
The present invention seeks to provide a test which can be readily performed in a relatively short time period after a suspected heart attack.
In addition it is now known that although free radicals are essential for many normal physiological processes, they can, however, become highly destructive If not tightly controlled. In the normal course of events cells and tissues have adequate antioxidant defences both intracellularly and extracellularly to deal with excess radical generation. However, any pathological situation which increases the turnover of the antioxidant cycle, whether increased oxidative stress or defective anti-radical defences, can lead to progressive membrane, cellular and tissue damage. Free radicals have been implicated in the pathophysiology of many disease states including rheumatoid arthritis, adult respiratory distress syndrome, thalassaemia, reperfusion injury, atherosclerosis and ischaemic heart disease. The formation of oxygen-derived free radicals occurs as an accompaniment to or a consequence of the initial pathology thus exacerabating the primary lesion.
There is also the possibility of further damage occurring at the time of reperfusion. There is now a wide range of evidence linking oxygen-derived free radicals to cardiovascular disease and myocardial post-ischaemic reperfusion injury. Normally, the tissue concentration of active oxygen species is limited and the aerobic myocardium survives because of the existence of a delicate balance between the cellular systems that generate the various oxidants in the normal course of events and those that maintain the antioxidant defence mechanisms.
It will be seen therefore that there is a need to monitor the antioxidant defenses, which may be limited, in disease states or in states which would lead to problems, e.g. pre-term babies. Furthermore, there is a need for ready
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American Heart Journal, vol. 105, No. 4, 4/83 pp. 642-651 Drexel et al "Myoglobinemia in the early..myocardial infarction".
Hochstein, P. "Antioxidant Mechanisms in the Heart. The potential involvement of Myoglobin", pp. 245-252, contained in book by Labbate et al., Role of oxygen radicals in Cardiovascular Disease, 1988.
Davies Michael J.
Rice-Evans Catherine A.
British Technology Group Limited
Housel James C.
Wallenhorst Maureen M.
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